The association between use of proton pump inhibitors and frailty index among middle-aged and older adults.

Aims: This study aimed to investigate the association between use of proton pump inhibitors (PPI) and frailty index (FI), and to assess the causality relationship using Mendelian randomization (MR).

Methods: A total of 9756 middle-aged and older adults from the National Health and Nutrition Examination Survey were included. The FI was evaluated using a previously validated 49-item deficit model to assess frailty status, which is one of the common approaches to measure overall health burden. We performed weighted multivariable-adjusted linear regression to assess the association between PPI use and FI, and conducted a two-sample MR to evaluate causality, employing various sensitivity analyses for robustness. The inverse variance weighted (IVW) method was used as the primary analysis.

Results: Multiple linear regression analysis revealed a positive association between PPI use and FI (β = 0.048, 95% confidence interval [CI]: 0.042-0.054, P < .001). This association was observed in both short-term (≤ 1 year) and long-term (> 1 year) PPI users (P for trend < 0.001). The MR study also revealed a positive association between PPI use and FI based on the IVW method (β = 1.183, 95% CI: 0.474-1.892, P = .001).

Conclusions: While our findings suggest a potential link between PPI use and FI, they should be interpreted with caution due to the study's limitations. Although the MR analysis suggests a causal relationship, further research, particularly longitudinal studies, is needed to confirm these findings and better establish temporality.